rs1057518748
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP5
The NM_138773.4(SLC25A46):c.1005A>T(p.Glu335Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
SLC25A46
NM_138773.4 missense
NM_138773.4 missense
Scores
2
10
6
Clinical Significance
Conservation
PhyloP100: 1.22
Genes affected
SLC25A46 (HGNC:25198): (solute carrier family 25 member 46) This gene encodes a mitochondrial solute carrier protein family member. It functions in promoting mitochondrial fission, and prevents the formation of hyperfilamentous mitochondria. Mutation of this gene results in neuropathy and optic atrophy. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM1
?
In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_138773.4
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 5-110761530-A-T is Pathogenic according to our data. Variant chr5-110761530-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 372239.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC25A46 | NM_138773.4 | c.1005A>T | p.Glu335Asp | missense_variant | 8/8 | ENST00000355943.8 | |
SLC25A46 | NM_001303249.3 | c.762A>T | p.Glu254Asp | missense_variant | 8/8 | ||
SLC25A46 | NM_001303250.3 | c.732A>T | p.Glu244Asp | missense_variant | 8/8 | ||
SLC25A46 | NR_138151.2 | n.1244A>T | non_coding_transcript_exon_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A46 | ENST00000355943.8 | c.1005A>T | p.Glu335Asp | missense_variant | 8/8 | 1 | NM_138773.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Neuropathy, hereditary motor and sensory, type 6B Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 14, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;T;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
1.0
.;D;.;.;.
Vest4
MutPred
0.58
.;Gain of relative solvent accessibility (P = 0.0479);.;.;.;
MVP
MPC
0.32
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at